1CZQ

CRYSTAL STRUCTURE OF THE D10-P1/IQN17 COMPLEX: A D-PEPTIDE INHIBITOR OF HIV-1 ENTRY BOUND TO THE GP41 COILED-COIL POCKET.

Summary for 1CZQ

• Entry DOI: 10.2210/pdb1czq/pdb
• Descriptor: FUSION PROTEIN BETWEEN THE HYDROPHOBIC POCKET OF HIV GP41 AND GCN4-PIQI, D-PEPTIDE INHIBITOR, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: envelope glycoprotein, viral protein-inhibitor complex, viral protein/inhibitor
• Biological source: Saccharomyces cerevisiae, Human immunodeficiency virus (baker's yeast,); More
• Total number of polymer chains: 2
• Total formula weight: 7363.14

Authors

Eckert, D.M.,Malashkevich, V.N.,Hong, L.H.,Carr, P.A.,Kim, P.S. (deposition date: 1999-09-06, release date: 1999-10-13, Last modification date: 2024-11-13)

Primary citation

Eckert, D.M.,Malashkevich, V.N.,Hong, L.H.,Carr, P.A.,Kim, P.S.
Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket.
Cell(Cambridge,Mass.), 99:103-115, 1999

PubMed Abstract: The HIV-1 gp41 protein promotes viral entry by mediating the fusion of viral and cellular membranes. A prominent pocket on the surface of a central trimeric coiled coil within gp41 was previously identified as a potential target for drugs that inhibit HIV-1 entry. We designed a peptide, IQN17, which properly presents this pocket. Utilizing IQN17 and mirror-image phage display, we identified cyclic, D-peptide inhibitors of HIV-1 infection that share a sequence motif. A 1.5 A cocrystal structure of IQN17 in complex with a D-peptide, and NMR studies, show that conserved residues of these inhibitors make intimate contact with the gp41 pocket. Our studies validate the pocket per se as a target for drug development. IQN17 and these D-peptide inhibitors are likely to be useful for development and identification of a new class of orally bioavailable anti-HIV drugs.

PubMed: 10520998
DOI: 10.1016/S0092-8674(00)80066-5

Experimental method

X-RAY DIFFRACTION (1.5 Å)